UV blocker loaded contact lenses

ABSTRACT

UV absorbing appliances, such as contact lenses, are prepared by including at least one UV absorbing compound in the appliances. UV absorbing compounds can be water insoluble and/or reside in UV absorbing nanoparticles having a mean diameter less than 10 nm. The UV absorbing nanoparticles incorporate into an appliance by polymerizing a monomer mixture containing the UV absorbing nanoparticles to form an appliance comprising the UV absorbing nanoparticles. The UV absorbing compounds or the UV absorbing nanoparticles incorporate into an appliance by placing the appliance in a solution of the UV absorbing compound or a dispersion of the UV absorbing nanoparticles in a non-aqueous solvent that swells the appliance. The UV absorbing compound or the UV absorbing nanoparticles infuse into the swollen appliance and are retained within the appliance upon removal of the non-aqueous solvent.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No.14/296,899, filed Jun. 5, 2014, now U.S. Pat. No. 9,594,188, which is acontinuation-in-part of International Patent Application No.PCT/US2012/068084, filed Dec. 6, 2012, which claims the benefit of U.S.Provisional Patent Application Ser. No. 61/567,517, filed Dec. 6, 2011,and U.S. application Ser. No. 14/296,899 claims the benefit of U.S.Provisional Patent Application Ser. No. 61/860,568, filed Jul. 31, 2013,the disclosures of which are hereby incorporated by reference in, theirentirety.

BACKGROUND OF THE INVENTION

Exposure to the ultraviolet radiation from the sun has the potential tocause significant damage to the body including skin irritation, burning,and skin cancer. It has become a very common practice to use UV blockinglotions and creams to minimize the damage from sun exposure. While thegeneral population is well aware of the potential for damage to skinfrom UV radiation, there is less awareness of the possibility of damageto other organs, particularly eyes. There is a growing concern thatcontinuous exposure of UV radiation to eyes could cause serious medicalproblems including cataract and retina damage. UV radiation can causemild irritation and a foreign body sensation in the eyes. Regular UVexposure can cause blindness, cataracts, photokeratitis, erythema of theeyelid, solar retinopathy, retinal damage, and cancer of cornea orconjunctiva. Damage from the UV radiation is likely due to free radicalformation that causes protein modification and lipid peroxidation. Theintraocular lens of an adult eye filters a majority of the UV light,whereas the lens of an infant's eye transmits nearly all of the UVlight. UV transmittance decreases with age, and by the age of 25 nearlyall UV light is absorbed by the lens. Accumulated exposure to UV lightby the age of 25 could cause significant retinal damage.

UV damage can be minimized by wearing eye glasses or contact lenses thatare protective against peripheral radiation. The degree of blockinghowever depends on the type of lenses and the design of the sunglasses.Most styles of sunglasses do not offer complete protection from UVradiation, allowing UV light to reach the eyes around the frames of theeyeglasses. Wearing UV blocking contact lenses, which cover the entirecornea, can provide UV protection from all angles.

The U.S. Food and Drug administration (FDA) has established standardsfor UV blocking contact lenses based on American National StandardsInstitute (ANSI) standards, and classifies UV blocking contact lensesinto two categories (Class 1 and Class 2) depending on the extent of theprotection. Class 1 lenses must block more than 90% of UVA and 99% ofUVB (280-315 nm) radiation. Class 2 lenses must block more than 70% ofUVA and 95% of UVB radiation. Although UVA radiation corresponds to thewavelength range of 315-400 nm, only wavelengths from 315-380 nm areconsidered for classification of a contact lens. Only three commercialcontact lenses (ACUVUE® Oasys™, ACUVUE® Advance® and ACUVUE® Advance forAstigmatism) are categorized as Class 1 blocking lenses.

UV blocking by contact lenses is achieved by adding a UV absorbingmolecule to the lens composition. UV absorbers and the preparation of UVblocking contact lenses has primarily involved monomeric UV absorbersthat contain an acrylic or styrenic group for copolymerization with thelens forming material, for example: Loshaek, U.S. Pat. No. Re. 33,477;Dunks et al., U.S. Pat. No. 4,716,234; Bambury et al., U.S. Pat. No.4,719,248; Jinkerson, U.S. Pat. No. 5,470,932; Jinkerson, U.S. Pat. No.5,543,504; Collins et al., U.S. Pat. No. 5,637,726; Haywood et al., U.S.Pat. No. 7,364,291; and Jinkerson et al., U.S. Pat. No. 7,803,359. Honget al., U.S. Pat. No. 6,914,086 teaches a crosslinkable UV absorber witha plurality of polymerizable vinyl groups for incorporation bycopolymerization with the lens forming material. Hung et al., U.S. Pat.No. 4,963,160 teaches the absorption of an acid salt comprising anabsorber on a contact lens followed by neutralization and extractionuntil only surface bound UV absorbers remain on the lenses. Fabricationof UV absorber containing contact lenses, or the contact lensesthemselves, often suffer from one or more undesired features such as:long reacting times; low conversions; uncertainty in the degree ofreaction; leach of unreacted UV absorber; yellowness; inconsistentintegrity of the formed lens; expensive reactants; and tedious reactingprocess.

The major challenges in preparing a contact lens loaded with a UVabsorber remain preparing the lens with short curing times at reasonablelight intensities to avoid any undesired side reactions, maintaining theclarity and uniformity of the lens and the Absorber over the entire areaof the lens, and avoiding any leaching of UV absorber from the lens. Ascurrently there are only a few commercially available contact lensesthat are approved as Class 1 UV blockers, there remains a need todevelop effective UV blocking contact lenses.

BRIEF SUMMARY OF THE INVENTION

An embodiment of the invention is directed to a UV absorbing compoundand UV absorbing nanoparticle comprising a UV absorbing compounddispersed in a cross-linked gel. The gel has a high cross-link densitysuch that the UV absorbing compound can not diffuse from the gel. The UVabsorbing nanoparticles have a mean cross-section that is less than 10nm. The UV absorbing compound, for example,1,3-diphenyl-1,3-propanedione (DP), absorbs light in the UVA, UVB andUVC regions of the electromagnetic spectrum. In an embodiment of theinvention, the UV absorbing compounds in the nanoparticles are reactedand unreacted 1,3-diphenyl-1,3-propanedione (DP) and2-(4-Benzoyl-3-hydroxyphenoxy)ethyl acrylate (BHPEA). The gel is thecross-linked product from the polymerization of an alkene containingmonomer or monomer mixture, where the average monomer has at least twopolymerizable alkene groups. In an exemplary embodiment of theinvention, the alkene comprising monomer is propoxylated glyceryltriacrylate (PGT).

In an embodiment of the invention, the UV absorbing nanoparticles areprepared by polymerizing a mixture of: at least one alkene comprisingmonomer, where the average monomer has a plurality of alkene units; afree radical initiator; a plurality of UV absorbing compounds; and atleast one chain transfer agent. The polymerization is stopped beforecomplete gelation, a solvent is added, and dialysis is performed toseparate the UV absorbing nanoparticles from any unreacted orunincorporated components of the polymerization mixture. In an exemplaryembodiment of the invention, the alkene comprising monomer ispropoxylated glyceryl triacrylate (PGT), the chain transfer agent isisooctyl 3-mercaptopropionate (CTA), the UV absorbing compounds are1,3-diphenyl-1,3-propanedione (DP) and2-(4-Benzoyl-3-hydroxyphenoxy)ethyl acrylate (BHPEA), and the freeradical initiator is benzoyl peroxide.

Another embodiment of the invention is a UV blocking appliancecomprising the UV absorbing nanoparticles described above. The appliancecan be a hydrophilic gel or silicone-hydrogel; for example, theappliance can be a contact lens.

Another embodiment of the invention is a UV blocking appliancecomprising the UV absorbing compound infused into a hydrophilic gel orsilicone-hydrogel appliance, for example, a contact lens. Anotherembodiment of the invention is a method to form the UV blockingappliance comprising the UV absorbing compound. The method comprisessoaking a UV blocking appliance in a solution comprising the UVabsorbing compound and a solvent that swells the appliance.

Another embodiment of the invention is a method for the preparation ofthe UV absorbing nanoparticles described above, where monomers having,on average, a plurality of polymerizable alkene groups per monomer, arecombined with a free radical initiator, a UV absorbing compound, and adiluent and the combined mixture is polymerized in a non-aqueous solventsystem or in an emulsion system comprising a surfactant and a aqueoussolution. The diluent can be an oil, for example, vitamin E. The UVabsorbing nanoparticles can be separated from the polymerization mixtureby centrifugation.

Another embodiment of the invention is a method for the preparation ofthe UV blocking appliance by polymerizing alkene comprising monomers toa gel, where the average number of alkene groups per monomer is greaterthan 1, in a free radical polymerization with the UV absorbingnanoparticles included in the polymerization mixture. An initiator isincluded that can be activated either by photolysis or thermolysis.

Another embodiment of the invention is a method for the preparation ofthe UV blocking appliance by soaking a gel appliance, such as a contactlens, in a suspension of the UV absorbing nanoparticles. The suspendingliquid is a non-aqueous solvent that swells the gel appliance permittingdiffusion of the UV absorbing nanoparticles into the appliance. The UVabsorbing nanoparticles are trapped in the appliance upon removal of thenon-aqueous solvent. The non-aqueous solvent can be removed from theswollen appliance as a volatile or can be extracted into an aqueoussolution or water to trap the UV absorbing nanoparticles in the UVblocking appliance.

In an embodiment of the invention, the UV blocking appliance is formedby polymerizing an alkene comprising monomer mixture having amultiplicity of UV absorbing nanoparticles, and a free radicalinitiator. The free radical initiator can be a photoinitiator or athermal initiator. In another embodiment of the invention, the UVblocking appliance is formed by soaking a hydrophilic orsilicone-hydrogel appliance in a non-aqueous dispersion of UV absorbingnanoparticles such that the nanoparticles can enter the swollenappliance and are trapped within the appliance upon removing of thesolvent from the swollen apparatus.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1C are schematic illustrations of the mechanism of formation ofhighly crosslinked nanoparticles in the presence of a diluent where FIG.1A shows an emulsion micelle shown at early stages of polymerization,which evolves; FIG. 1B shows an emulsion micelle containing severalnanoparticles with high concentration of diluents in the unpolymerizedliquid; and FIG. 1C shows a final emulsion with several micellescontaining several nanoparticles.

FIG. 2 shows the chemical structure of UV absorbing compounds1,3-diphenyl-1,3-propanedione (DP) and2-(4-Benzoyl-3-hydroxyphenoxy)ethyl acrylate (BHPEA), which areincorporated into UV absorbing nanoparticles, according to an embodimentof the invention.

FIG. 3 shows the UV spectra of DP and BHPEA in ethanol and salinesolution (PBS).

FIG. 4 shows the mean particle size for UV absorbing nanoparticles,according to an embodiment of the invention, having different BPloadings with the compositions given in Table 1.

FIG. 5 shows percent transmittance spectra for appliances according toan embodiment of the invention formed from soaking an O2OPTIX® siliconhydrogel lens in a 0.7% w/w solution of 1,3-diphenyl-1,3-propanedione(DP) in ethanol, according to an embodiment of the invention.

FIG. 6 shows percent transmittance spectra for appliances according toan embodiment of the invention fonned from 1% DP containingnanoparticles dispersions in a silicone polymerization mixture atvarious nanoparticle contents and for DP free nanoparticles relative toa control appliance free of nanoparticles.

FIG. 7 shows percent transmittance spectra for appliances according toan embodiment of the invention formed from 2.6% DP containingnanoparticles dispersed in silicone polymerization mixture at differentnanoparticle concentrations relative to a control appliance free ofnanoparticles.

FIG. 8 shows percent transmittance spectra for appliances according toan embodiment of the invention formed from 5.9% DP containingnanoparticles dispersed in silicone polymerization mixture at differentnanoparticle concentrations relative to a control appliance free ofnanoparticles.

FIG. 9 shows a percent transmittance spectrum for appliances accordingto an embodiment of the invention formed from 9.7% DP containingnanoparticles dispersed in silicone polymerization mixture at a 5%nanoparticle concentration relative to a control appliance free ofnanoparticles.

FIG. 10 shows percent transmittance spectra for appliances according toan embodiment of the invention formed from 5.9% DP containingnanoparticles dispersed in silicone polymerization mixture at a 5%concentration before and after curing thermally at 100° C. for 2 hoursrelative to a control appliance free of nanoparticles.

FIG. 11 shows percent transmittance spectra for appliances according toan embodiment of the invention formed by soaking the appliance in 10.2%DP containing nanoparticles solutions in various concentrations ofethanol relative to a control appliance free of nanoparticles.

FIG. 12 shows percent transmittance spectra for appliances according toan embodiment of the invention formed by soaking the appliance in 15.8%DP containing nanoparticles solutions in various concentrations ofethanol relative to a control appliance free of nanoparticles.

FIG. 13 shows percent transmittance spectra for appliances according toan embodiment of the invention formed by soaking the appliance in 19.6%DP containing nanoparticles solutions in various concentrations ofethanol relative to a control appliance free of nanoparticles.

FIG. 14 shows percent transmittance spectra for appliances according toan embodiment of the invention formed by soaking the appliance in 28.1%DP containing nanoparticles solutions in various concentrations ofethanol relative to a control appliance free of nanoparticles.

FIG. 15 shows percent transmittance spectra for autoclaved appliancesaccording to an embodiment of the invention formed by soaking theappliance in 15.8% DP containing nanoparticles solutions in variousconcentrations of ethanol relative to a control appliance free ofnanoparticles.

FIG. 16 shows composite UV transmittance spectra for Night & Day contactlenses loaded with the UV absorbing nanoparticles of Table 4 for 5minutes, according to an embodiment of the invention.

FIG. 17 shows UV spectra of UV absorbing compounds released from Night &Day contact lenses of the compositions given in Table 6 into PBSsolution, according to an embodiment of the invention.

FIG. 18 shows percent transmittance spectra for appliances according toan embodiment of the invention formed by soaking the appliance in 15.8%DP containing nanoparticles solutions in various concentrations ofethanol relative to a control appliance free of nanoparticles wherenanoparticles were as prepared or after autoclaving.

FIG. 19 shows a UV transmittance spectrum for a Night & Day contact lensloaded with UV absorbing nanoparticles before and after autoclaving,according to an embodiment of the invention.

FIG. 20 shows percent transmittance spectra for appliances according toan embodiment of the invention formed by soaking Night and Day® contactlenses in 19.6% DP containing nanoparticles solutions in variousconcentrations of ethanol relative to a control appliance free ofnanoparticles where lenses were as solution treated or after autoclavingthe solution treated lenses.

FIG. 21 shows percent transmittance spectra for appliances according toan embodiment of the invention formed by soaking PureVision® contactlenses in 19.6% DP containing nanoparticles solutions in variousconcentrations of ethanol relative to a control appliance free ofnanoparticles where lenses were as solution treated or after autoclavingthe solution treated lenses.

DETAILED DESCRIPTION OF THE INVENTION

Embodiments of the invention are directed to UV absorbing appliancescomprising UV absorbing compounds infused in visibly transparentappliances, such as contact lenses. In an embodiment of the invention,the UV absorbing compound is absorbed in the UV blocking appliance bysoaking the appliance in a solution of the UV absorbing compound for asufficient period to partition the UV absorbing compound into theappliance and removing solvent absorbed by the UV absorbing appliance.

UV absorbing compounds that can be infused into swollen appliances, forexample commercially available contact lenses, which have a desiredstructure and cross-link density that is well established in theindustry, must be those which remain in the resulting UV absorbingappliance and are not readily partitioned into a aqueous solution or area compound that is benign or advantageous to an organism. In anembodiment of the invention, the UV absorbing compound is1,3-diphenyl-1,3-propanedione (DP). In an embodiment of the invention,the UV absorbing compounds are 1,3-diphenyl-1,3-propanedione (DP) and2-(4-Benzoyl-3-hydroxyphenoxy)ethyl acrylate (BHPEA).

Embodiments of the invention are directed to UV absorbing materialencapsulated in nanoparticles and appliances, such as contact lenses,including these UV absorbing nanoparticles to form the UV absorbingappliances. By use of the UV absorbing nanoparticles, UV absorbingcompounds are more permanently fixed within a UV absorbing appliancethan are any given UV absorbing compound that is not fixed in ananoparticle. The UV absorbing nanoparticles comprise any availablemonomeric or oligomeric UV absorbing compound where the absorber islocked within a highly crosslinked nanoparticle such that leaching ofthe UV absorber can not occur from the nanoparticle, and, therefore,from any appliance in which it is incorporated, such as, but not limitedto, a lens. In one embodiment, as shown in FIG. 1, a highly crosslinkednanoparticle is formed in the presence of a diluent where (a) anemulsion micelle evolves into (b) an emulsion micelle containing severalnanoparticles with high concentration of diluents in an unpolymerizedliquid, and (c) finally evolves into an emulsion with several micellescontaining several nanoparticles.

In an embodiment of the invention, two UV blocking molecules areincluded in the nanoparticle formulation to maximize blocking of UVA andUVB radiation. The two molecules 1,3-diphenylpropane-1,3-dione (DP) and2-(4-Benzoyl-3-hydroxyphenoxy)ethyl acrylate (BHPEA), as shown in FIG.2, are optimal for blocking UVA and UVB, respectively. A formulationwith these two molecules is optimal for achieving Class 1 UV blockingwith minimal loading. BHPEA can be polymerized into the nanoparticlestructure and, therefore, will not diffuse from the lens on insertion inthe eye. Similarly, DP acts as a chain transfer agent, as it is capablelosing a hydrogen atom to form a free radical that initiates a chain andcovalently attaches to the particle. Furthermore, DP is highlyhydrophobic and free DP release into tears is minimal. In an embodimentof the invention, a very small pore size rigid particle is formed byusing a tri-functional monomer for the preparation of the particles. DPis highly biocompatible with useful medical properties, includingpotential benefits in cancer prevention and therapy.

In an embodiment of the invention, the UV absorbing nanoparticlescomprising appliances can be formed by inclusion of the nanoparticles inthe polymerization mixtures that form the appliances. In anotherembodiment of the invention, the nanoparticles, when sufficiently small,can be infused into the formed appliance in a solution process. Theparticles can be loaded into the appliance from a medium comprising anon-aqueous, but water soluble, solvent that sufficiently swells atleast a portion of the lens to allow the nanoparticles to diffuse intothe appliance. After particle loading, the appliance is soaked in anaqueous solution, for example, a saline solution, to extract the loadingmedium. As the loading medium is extracted, the medium swollen pores ofthe appliance contract to dimensions that trap the UV absorbingnanoparticles within the appliance. The trapped particles cannot diffusefrom the appliance into the aqueous solution because the non-aqueoussolvent is rapidly lost from the swollen appliance relative to the rateof migration of the UV absorbing nanoparticles through the pores of theappliance, such that the decreasing pore size achieved does not permitdiffusion from the appliance after extraction of the non-aqueoussolvent.

According to an embodiment of the invention, the bulk or surfacecomposition of the UV absorbing nanoparticles can be matched to thestructure of a portion of the appliance, for example, a nanoparticle gelcomposition that displays a complementary hydrophobicity, charge, orother property that promotes the nanoparticle's interaction with amaterial within the appliance. This unique approach of loading the UVabsorber to a prepared contact lens, or other UV absorbing appliance,allows the lens to be prepared as is currently carried out withoutconcern of unfavorable consequences in the rate, degree, or uniformityof curing imposed on the established process.

UV absorbing nanoparticles that can be infused into swollen appliances,for example, commercially available contact lenses, which have a desiredstructure and cross-link density that is well established in theindustry, must be extremely small. UV absorbing nanoparticles, accordingto an embodiment of the invention are less than about 10 nm incross-section, and are highly crosslinked such that no significantswelling of the nanoparticles occurs during swelling and delivery of theUV absorbing nanoparticles. Additionally, the very high cross-linkdensity also assures that UV absorbers do not diffuse from thenanoparticle. According to an embodiment of the invention, the UVabsorbing nanoparticles are formed by a surfactant free process.

The contact lens material can be a silicone hydrogel as described inInternational Application No. PCT/US2008/065325; filed May 30, 2008,published on Dec. 11, 2008 as WO 2008/151019 and hereby incorporated byreference herein in its entirety, including any figures, tables, ordrawings. The contact lens material can also be any material used insoft contact lenses; such a hydroxyethylmethacrylate (HEMA) basedlenses. The contact lens material can be a single phase, as in ahomopolymer or random copolymer, or can consist of a plurality ofdiscontinuous phases as is common of many block copolymers, such assilicone hydrogels. Commercially available silicone hydrogel contactlenses can be employed in embodiments of the invention. Siliconehydrogel contact lenses that are available commercially including:ACUVUE® ADVANCE™ (Johnson & Johnson Vision Care, Inc., Jacksonville,Fla.); ACUVUE® OASYS™ (Johnson & Johnson Vision Care, Inc.,Jacksonville, Fla.); NIGHT&DAY™ (Ciba Vision Corp., Duluth, Ga.);O₂OPTIX™ (Ciba Vision Corp., Duluth, Ga.); and PureVision™ (Bausch &Lomb, Inc., Rochester, N.Y.). The commercially available lenses can bemodified by incorporating the UV absorbing nanoparticles.

Silicone hydrogels can be prepared in a manner similar to that common topreparation of such networks, where hydrophobic silicon containingmonomers are included into the formulation and the silicone monomer iscopolymerized with monomers to provide hydrophilic character to theresulting network. Usually a silicone monomer that can undergo additioninto the growing polymer at two sites or more is included. Such siliconehydrogels are non-homogeneous structures, often displaying discernablephase separation between a silicone rich phase and a hydrophilic monomerderived phase. Depending upon the nature of these hydrogels, surfacetreatment is sometimes necessary to assure the surface is sufficientlyhydrophilic even though these hydrogels are designed to incorporate 20to more than 80 percent by weight water. Surface treatment can includecoating with a hydrophilic coating or plasma etching to convert thesilicon surface into a hydroxy group rich silicate type surface.

Suitable silicone hydrogel materials include, without limitation,silicone hydrogels made from silicone macromers such as thepolydimethylsiloxane methacrylated with pendant hydrophilic groupsdescribed in U.S. Pat. Nos. 4,259,467; 4,260,725 and 4,261,875; or thepolydimethylsiloxane macromers with polymerizable functional describedin U.S. Pat. Nos. 4,136,250; 4,153,641; 4,189,546; 4,182,822; 4,343,927;4,254,248; 4,355,147; 4,276,402; 4,327,203; 4,341,889; 4,486,577;4,605,712; 4,543,398; 4,661,575; 4,703,097; 4,740,533; 4,837,289;4,954,586; 4,954,587; 5,034,461; 5,070,215; 5,260,000; 5,310,779;5,346,946; 5,352,714; 5,358,995; 5,387,632; 5,451,617; 5,486,579;5,962,548; 5,981,615; 5,981,675; and 6,039,913. The silicone hydrogelscan also be made using polysiloxane macromers incorporating hydrophilicmonomers such as those described in U.S. Pat. Nos. 5,010,141; 5,057,578;5,314,960; 5,371,147; and 5,336,797; or macromers comprisingpolydimethylsiloxane blocks and polyether blocks such as those describedin U.S. Pat. Nos. 4,871,785 and 5,034,461. All of the cited patents arehereby incorporated in their entireties by reference.

Among the silicone containing monomers which may be in the formulationof a silicone hydrogel of the present invention includeoligosiloxanylsilylalkyl acrylates and methacrylates containing from2-10 Si-atoms. Typical representatives include:tris(trimethylsiloxysilyl)propylmethacrylate,triphenyldimethyldisiloxanylmethylmeth-acrylate,pentamethyldisiloxanylmethylmethacrylate,tert-butyltetramethyldisiloxanyl-ethyl-methacrylate,methyldi(trimethylsiloxy)silylpropylglycerylmethacrylate;penta-methyldisiloxanylmethylmethacrylate;heptamethylcyclotetrasiloxanylmethylmeth-acrylate;hepta-methylcyclotetrasiloxanylpropylmethacrylate;(trimethylsilyl)decamethyl-pentasiloxanylpropylmethacrylate;undecamethylpentasiloxanylpropylmethacrylate; and the acrylateequivalents of these methacrylates.

Other representative silicon-containing monomers which may be used forsilicone hydrogels of the present invention include silicone-containingvinyl carbonate or vinyl carbamate monomers such as:1,3-bis[4-vinyloxycarbonyloxy)but-1-yl]tetramethyldi-siloxane;3-(trimethylsilyl)propyl vinyl carbonate;3-(vinyloxycarbonylthio)propyl[tris-(trimethylsiloxy)silane];3-[tris(trimethylsiloxy)silyl] propyl vinyl carbamate;3-[tris(trimethylsiloxy)silyl] propyl allyl carbamate;3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate;t-butyldimethylsiloxethyl vinyl carbonate; trimethylsilylethyl vinylcarbonate; and trimethylsilylmethyl vinyl carbonate.Polyurethane-polysiloxane macromonomers (also sometimes referred to asprepolymers), which have hard-soft-hard blocks like traditional urethaneelastomers, may be used. Examples of such silicone urethanes which maybe included in the formulations of the present invention are disclosedin a variety or publications, including Lai, Yu-Chin, “The Role of BulkyPolysiloxanylalkyl Methacrylates in Polyurethane-PolysiloxaneHydrogels,” Journal of Applied Polymer Science, Vol. 60, 1193-1199(1996).

Suitable hydrophilic monomers that may be used separately or incombination for the silicone hydrogels of the present inventionnon-exclusively include, for example: unsaturated carboxylic acids, suchas methacrylic and acrylic acids; acrylic substituted alcohols, such as2-hydroxyethylmethacrylate, 2-hydroxyethylacrylate (HEMA), andtetraethyleneglycol dimethacrylate (TEGDMA); vinyl lactams, such asN-vinyl pyrrolidone; vinyl oxazolones, such as2-vinyl-4,4′-dimethyl-2-oxazolin-5-one; and acrylamides, such asmethacrylamide; and N,N-dimethylacrylamide (DMA). Still further examplesare the hydrophilic vinyl carbonate or vinyl carbamate monomersdisclosed in U.S. Pat. No. 5,070,215, and the hydrophilic oxazolonemonomers disclosed in U.S. Pat. No. 4,910,277. Hydrophilic monomers maybe incorporated into such copolymers, including, methacrylic acid,2-hydroxyethylmethacrylamide.

The proportions of the monomers can vary over a large range. Thepolymerization mixtures can also include effective amounts of additives,initiators, photoinitiators, and/or catalysts and the reaction can beconducted in the presence of a diluent. Activation of the initiator forpolymerization can be by thermal or photochemical means. Thepolymerization can occur via any ionic, radical or group transfermechanism.

In embodiments of the invention, the UV absorbing appliances containingthe UV absorbing compounds or UV absorbing nanoparticles can be used asa dosage form for delivering bioactive agents. Bioactive agents caninclude ocular drugs and nutraceuticals. Suitable drugs or mixtures ofdrugs for delivery by the contact lenses can be selected from, but arenot limited to: glaucoma drugs such as timolol, pilocarpine,latanoprost; steroids such as dexamethasone and prednisilone;immunosuppressants such as cyclosporine; antibiotics such asciprofloxacin, ciloxan and gentamycin; antiallergy drugs such ketotifen;and antiparisitic and antiprotzoal drugs such as ivermectin, andpyrimethamine. A nutraceutical or mixtures of nutraceuticals fordelivery by the contact lenses can be selected from, but are not limitedto: Vitamin B-1; Vitamin B-2; Vitamin B-3; Vitamin B-5; panthenol;pantothenic acid; Vitamin B-6; Vitamin B-8; Vitamin B-9; Vitamin B-12;Cobalamin; Folic Acid; Biotin; Choline Inositol; Para Amino BenzoicAcid; Ascorbic Acid; Vitamin C; Beta Carotene; Vitamin D; Vitamin E;Calcium; and salts that provide ionic Copper, Chromium, Iodine, Iron,Manganese, Magnesium, Molybdenum, Phosphorous, Potassium, Sodium,Selenium, and Zinc; colloidal minerals; chelated minerals; and RDAminerals. Mixtures of drugs and nutraceuticals can be delivered by thecontact lens dosage form. Nutraceuticals are any non-drug compound thathas a physiologically beneficial effect on the eye by improving thehealth of the eye or specifically preventing an ocular disease. Inaddition, some nutraceuticals, such as vitamin E, can impart alubricating effect to reduce friction between the lens and the eye. Thebioactive agents can be loaded in a manner where they are directlyabsorbed in the appliance, or where the bioactive agent is incorporatedin a microparticle or a nanoparticle that can bi included in theappliance in a polymerization mixture for formation of the appliance, orby diffusion of nanoparticles into a preformed appliance. Themicroparticles or nanoparticles can be formed from one or more monomersthat comprise, for example, the silicone or hydrogel phase of thesilicone-hydrogel appliance. In general, the microparticles ornanoparticles will be of a different composition or cross-link densitythat is its compatible phase in a silicone-hydrogel appliance such as toattenuate its diffusion from the appliance when used for delivery of thebioactive agent.

It was discovered that, as with the UV absorbing compounds, UV absorbingnanoparticles can be loaded into an appliance, by soaking the lenses insolutions of the compounds in organic solvents such as ethanol.Non-limiting examples of such organic solvents include ethanol, ethylacetate, butyl acetate isopropanol, n-propanol, DMSO, methanol, toluene,methylene chloride, and tetrahydrofuran. In general, the solvent shouldbe one that has a low toxicity, is non-carcinogenic, and isnon-mutanogenic or can be removed essentially in total from the siliconehydrogel by means commonly employed by those skilled in the art. Manyhydrophobic compounds have some solubility in ethanol and so thissolvent is most convenient. The solvents are generally, but notnecessarily, removed prior to placement of the hydrogel into the ocularenvironment or other tissue to be treated. The solvent can be removed asa volatile off-gassing from the hydrogel and can be assisted separatelyor by any combination of vacuum, heating, and a gas stream.

In embodiments of the invention, diffusion barriers can be included inthe UV absorbing appliance to decrease the rate of diffusion of anybioactive agent incorporated in the appliance with the UV absorbingnanoparticles. The diffusion attenuator can be any material where thebioactive agent has a sufficiently smaller diffusivity than itsdiffusivity in the contact lens material. The diffusion barriers can bea liquid or a solid. The diffusion attenuator material can be similar tothe lens material, only differing, for example, by the repeating unitcomposition of a copolymer or by the cross-linking density, for example,a higher cross-link density, from that of the polymeric material used asthe contact lens material. Diffusion attenuators can be diffusionbarriers that can have many different shapes, for example disc, plates,spheroids, needles, rods, spheres and/or irregular flake.

MATERIALS AND METHODS

Materials

N,N-Dimethylacrylamide (DMA), 1-vinyl-2-pyrrolidone (NVP), Dulbecco'sphosphate buffered saline (PBS) were purchased from Aldrich Chemicals(St Louis, Mo.). Propoxylated glyceryl triacrylate (PGT) was purchasedfrom Sartomer; Benzoyl peroxide (BP) (97%) and1,3-diphenyl-1,3-propanedione (DP) were purchased from Aldrich Chemicals(Milwaukee, Wis.). The macromerbis-alpha,omega-(methacryloxypropyl)polydimethylsiloxane (Macromer) wassupplied by Clariant. 3-methacryloxypropyl-tris(trimethylsiloxy)silane(TRIS) was provided by Silar laboratories (Scotia, N.Y.). Methyacrylicacid (MAA) was purchased from Polysciences, Inc. (Wattingyon, Pa.).2,4,6-Trimethylbenzoyl-diphenyl-phosphineoxide (Darocur TPO) wasprovided by Ciba (Tarrytown, N.Y.). Vitamin E (D-alpha tocopherol,Covitol F1370) was provided by Cogins Corporation.

Transmittance Measurements

The transmittance of UV absorbing nanoparticle-laden silicone hydrogelswas measured using an UV-Vis spectrophotometer (Thermospectronic Genesys10 UV). After being hydrated by soaking in DI water overnight, lenseswere mounted on the outer surface of a quartz cuvette. The cuvette wasplaced in a spectrophotometer and transmittance was measured at thewavelength range from 200 nm to 480 nm. Transmittance data was used tocalculate the average absorption of UVC, UVB and UVA radiation, wherethe UVA range, is 315-380 nm as per ANSI classification and for theentire UVA spectrum of 315-400 nm.

The UV blocking potential of DP and BHPEA was characterized by measuringthe absorbance spectra in a UV-Vis spectrophotometer. Both moleculeshave limited solubility in water. The absorbance spectra was firstmeasured in ethanol at a concentration of 0.02 mg/mL and then in waterat a concentration of 0.001 mg/mL. The absorbance spectra (A(λ)) wasused to calculate the molar absorptivity (E) using the Beer Lambert law,i.e., A=εcl, where l=1 cm is the path length and c is the concentrationin solution. The molar absorptivities of both DP and BHPEA are plottedin FIG. 3.

Nanoparticle Preparation

The UV blocker 1,3-diphenyl-1,3-propanedione (DP) was incorporated intohighly crosslinked particles of propoxylated glyceryl triacrylate (PGT).Since PGT has three vinyl groups, nanoparticles of PGT will haveextremely small pore size, thereby trapping DP molecules irreversibly.The DP loaded PGT nanoparticles were prepared using a diluent as apolymerization modifier. Vitamin E was chosen as the diluent due to itshydrophobicity and biocompatibility. To prepare the nanoparticles, DP,PGT and Vitamin E were mixed in the desired ratios and added to 7.5 mgof polymerization initiator BP. The mixture was added to DI water,purged with nitrogen for 15 minutes to remove dissolved oxygen, andheated in an 80° C. hot water bath with stirring at 1100 rpm for 8hours. The thermal polymerization results in formation of UV blockingnanoparticles. The particles are separated from the suspension bycentrifugation for 15 min.

The compositions used for preparation of nanoparticles are listed inTables 1, below. In each composition, varying amounts of the UV dye, DP,were added to 120 mg of Vitamin E, 1 g of PGT and 7.5 mg of BP. Theamount of DP was varied from 10 to 210 mg to create particles with DPfractions ranging from about 1% to 15.8%. To further increase the DPfraction an increase of the Vitamin E fraction was needed. Accordingly,280 or 450 mg of DP was added to 150 mg Vitamin E, 1 g of PGT, and 7.5mg BP to produce nanoparticles with DP loadings of about 19.6 and 28.1%,respectively.

TABLE 1 Experimental design of particles in polymerization mixture. MassMass UV dye in UV Vitamin % particles particle dye E in silicone (%)(mg) (mg) hydrogel 1 10 120 5, 10 2.6 30 120 5, 10, 20 5.9 70 120 5, 109.7 120 120 5

Other nanoparticles were prepared by bulk polymerization of a tri vinylmonomer propoxylated glyceryl triacrylate (PGT), the two UV blockingmolecules, DP and BHPEA, and a chain transfer agent, isooctyl3-mercaptopropionate (CTA). UV blocking nanoparticles were formed bymixing PGT, BHPEA, DP, and isooctyl 3-mercaptopropionate in desiredratios along with 0.1% by weight benzoyl peroxide. As an example, amixture of 40% PGT, 40% chain transfer agent, 10% BHPEA and 10% DBM wasmade followed by addition of 0.1% initiator BP. N₂ was bubbled throughthe mixture for 15 minutes to remove oxygen followed by heating to 80°C. for 4 hours. In some cases, the polymerization time was reduced toavoid gelation.

Polymerization solutions containing the nanoparticles also containedunreacted components and small polymer chains. Two stages of dialysiswere used to remove the undesired components from the solution ofnanoparticles. In a first dialysis, the polymerized solution was placedinside a dialysis bag with 12,000 Da cutoff, and the bag was submergedin a mixture of 75% ethanol and 25% acetone for a period of 16 hours.After 16 hours, the solution inside the bag was withdrawn and placedinto a fresh dialysis bag for a second dialysis. In each stage, thevolume of the outer solution was 20 times the volume of the liquidinside the bag. After 16 hours of the second stage of the dialysis, theabsorbance spectra of the outer solution (A_(o)) and the solution in thebag (A_(i)) were measured to determine composition and conversion.

The absorbance spectra can be expressed as a sum of the absorbance fromvarious components in the solution, by the equation:A(λ)=(Σε_(i) c _(i))  Equation I,where ε_(i) and c_(i) are the molar absorptivity and concentration ofthe i^(th) component, l is the path length, and the sum is carried overall the components in the solution. Due to the very high absorbance fromBHPEA and DP, one can neglect the absorbance contributions from allother components. Since the molar absorptivity of BHPEA and DP are knownand l is fixed at 1 cm, the absorbance spectra depend on only theconcentrations of BHPEA and DP, according to the equation:A(λ)=(ε_(DBM) c _(DBM)+ε_(BHPEA) c _(BHPEA))l  Equation II.

The unknown concentrations can be determined by a least square fitbetween the measured absorbance and the absorbance based on the aboveequation for wavelengths ranging from 250 to 350 nm.

The concentrations of BHPEA and DP are determined in the solution fromthe bag and that from the outer solution. In general, only unreactedcomponents diffuse through the dialysis bag, and, therefore,concentrations of BHPEA and DP are higher in the solution in the bag.The difference between the inside and the outside concentrationrepresents the nanoparticle-incorporated concentrations. By dividing thenanoparticle incorporated concentrations of DP and BHPEA, we can obtainthe ratio of these two components in the nanoparticles. The solutionfrom inside the bag was used for measuring the particle sizedistribution by dynamic light scattering. Table 2, below, summarizes theformulations used for the particle preparation and Table 3, below,summarizes the concentrations of the two components in the inner andouter solutions after the second dialysis. Formulation 1 (F1) wasrepeated three times to check for reproducibility and twice using alarger reaction volume. Formulation 1 was used for loading particlesinto contact lenses. Table 2 includes the particle-incorporatedconcentration of the two components, and the mean particle size. Thesize distributions for representative formulations are included in FIG.4.

TABLE 2 Formulations used for particle preparation by wt % FormulationF1 F2 F3 F4 F5 F6 % BHPEA 10 10 10 10 10 10 % DP 10 10 5 5 5 1 % CTA 4010 20 30 40 40 % PGT 39.9 69.9 64.9 54.9 44.9 48.9 % Initiator 0.1 0.10.1 0.1 0.1 0.1

TABLE 3 Concentrations inside and outside dialysis bags, concentrationincorporated into particles, and particle size Formulation in mg/mL F1F1 Scale Up F2 F3 F4 E5 F6 BHPEA Inside 2.45 +/− 0.36 2.67 +/− 0.09 2.132.22 1.86 2.08 2.34 BHPEA outside 0.18 +/− 0.01  0.3 +/− 0.01 0.29 0.200.21 0.17 0.19 BHPEA incorporated 2.27 +/− 0.36 2.38 +/− 0.1 1.84 2.021.65 1.90 2.15 DP Inside 0.17 +/− 0.02 0.33 +/− 0.05 0.28 0.02 0.10 0.150.16 DP outside 0.12 +/− 0.01 0.25 +/− 0.01 0.29 0.02 0.08 0.12 0.11 DPincorporated 0.05 +/− 0.01 0.08 +/− 0.06 0.00 0.00 0.02 0.04 0.05Particle Size (nm) 7.57 2.66 10.44 5.70 4.10 4.04 10.9Particle Size Distribution

The highly crosslinked UV absorbing nanoparticles are hydrophobic andare either dispersed in non-aqueous liquids like ethanol or in watercontaining a surfactant for the measurements of particle sizedistribution. Both aqueous solutions and ethanol solutions weretransparent, suggesting that the particle size is less than thewavelength of visible light. A mean particle size of about 3.5 nm wasdetermined in both mediums. The size measurements clearly indicated thatthe size of the particles is independent of the size of the emulsiondrops, but is controlled by the effect of the diluent on thepolymerization dynamics. Not to be bound by theory, below is ahypothetical mechanism for the formation of diluent encapsulatednanoparticles when a mixture of hydrophobic oily monomer(multifunctional monomers) is polymerized in an oily diluent (vitaminE).

Mechanism for Particle Formation

Nanoparticle formation is consistent with free radical polymerization ofmultifunctional monomers, such as EGDMA or PGT, where intramolecularaddition occurs to form and grow individual polymer nanogels because thediluent has a much lower affinity for the growing polymer than for themonomer mixture, which promotes intramolecular addition overintermolecular addition. In the emulsion polymerization, severalnanogels form in each emulsion drop and each nanogel encapsulates someUV absorber, and excludes diluent to a large extent. Rapidly, thenanoparticles reactive alkene groups become sufficiently low such thatcoalescence of the nanogels ceases and the microdrops of the emulsioncontain a multiplicity of nanogel particles.

This nanoparticle preparation method requires a careful optimization ofthe type and concentration of diluents. If the diluents concentrationfalls below a critical value, the growing nanogels in each drop mergeand with polymerization result in a microgel of the size of the drop. Anumber of oils were successfully used as diluents, including vitamin E,olive oil, timolol base (a glaucoma drug), and1,3-diphenyl-1,3-propanedione (UV absorber).

Preparation of Silicone Gels

Extended wear contact lenses were prepared from silicone hydrogels toobtain high oxygen and ion diffusion. The silicone gels were synthesizedby free radical polymerization of a mixture of a silicone monomer with ahydrophilic monomer. Additionally a macromer is added to ensuresolubilization of the silicone and the hydrophilic monomers. Othercomponents such as NVP can be added to increase the water content. Asilicone hydrogel was prepared by combining 0.8 ml of macromer(bis-alpha,omega-(methacryloxypropyl) polydimethylsiloxane) with 0.56 mlof N,N-dimethylacrylamide (DMA), 0.24 ml of methacrylic acid (MAA), 0.8ml of 3-methacryloxypropyl-tris(trimethylsiloxy)silane (Tris), 0.12 mlof 1-vinyl-2-pyrrolidone (NVP) and 10 μl of propoxylated glyceryltriacrylate (PGT). The mixture was purged by bubbling nitrogen throughthe mixture for 15 minutes. After adding 0.012 g of the initiatorDarocur® TPO to the mixture with stirring for 5 minutes, the mixture waspoured between two glass plates separated by a 100 μm thick plasticspacer. The mold was placed on an Ultraviolet transilluminiator UVB-10(Ultra•Lum, Inc.) and irradiated with UVB light (305 nm) for 50 minutes.The molded gel was cut into circular pieces (about 1.65 cm in diameter)using a cork borer and dried in air overnight.

Preparation of UV Absorbing Appliances by Infusion of UV AbsorbingCompounds.

UV absorbing contact lenses were prepared by loading O2OPTIX® siliconehydrogel lenses with 1,3-diphenyl-1,3-propanedione (DP). The O2OPTIXlenses were soaked individually in 3 ml of ethanol solution of DP with aDP concentration of 0.7% w/w. After three hours of soaking, the lenseswere withdrawn and submerged in 200 ml of DI water for two hours, whichextracted ethanol from the silicon hydrogels. The lenses were gentlywiped and then stored in 5 ml of DI water. The transmittance of thelenses loaded with DP was measured by UV Vis spectrophotometry, wherethe resulting spectrum is shown in FIG. 5. The lenses were visible lighttransparent and exhibited strong UV blocking with an average blocking of99.05% of UVA and 96.37% of UVB allowing the lenses to be defined asClass 2 blocker. The absorbance in UVB region can be increased beyond99% by increasing the DP concentration in ethanol to about 2% making thelens a Class 1 blocker. The leaching of DP is very limited due to itsvery high hydrophobicity and very low solubility in aqueous medium.

Nanoparticles Added to the Polymerization Mixture

Silicone hydrogels with UV absorbing nanoparticles were prepared withvarying amounts of DP nanoparticles added to the composition describedabove. Specifically, 0.13, 0.25, or 0.504 g of DP loaded nanoparticleswere added to a mixture of 0.8 ml of macromer(bis-alpha,omega-(methacryloxypropyl) polydimethylsiloxane), 0.56 ml ofN,N-dimethylacrylamide (DMA), 0.24 ml of methacrylic acid (MAA), 0.8 mlof 3-methacryloxypropyl-tris(trimethylsiloxy)silane (Tris), 0.12 ml of1-vinyl-2-pyrrolidone (NVP), and 100 μl of Propoxylated glyceryltriacrylate (PGT). The mixture was purged by bubbling nitrogen throughthe mixture for 15 minutes. After adding 0.012 g of initiator (Darocur®TPO) with stirring for 5 minutes, the mixture was poured between twoglass plates separated by a 100 μm thick plastic spacer. The molds werethen placed on Ultraviolet (Ultra-Lum, Inc.) and irradiated with UVBlight (305 nm) for 2 hours. The duration of polymerization was chosen tobe longer due to the attenuation in UV intensity because of theabsorption by the UV absorbing particles. The conditions for DP loadingin the nanoparticles and the nanoparticle loading in the polymerizationmixture are presented in Table 1, above.

As the UV blocking particles inhibit UV initiated polymerization,thermally initiated polymerization was used in some cases to cure thegel. The mold was placed in an oven at 80° C. for 24 hrs to polymerizethe gel. The thermal polymerization was used for a 5% UV absorbingnanoparticle loading where the nanoparticles contained 5.9% DP, and thethickness of the molded gel was 200 microns.

Loading UV Blocking Nanoparticles into Preformed Contact Lenses

After the second dialysis, the solution in the bag was directly used forthe contact lens loading or was concentrated by evaporation of thesolvent. Night & Day™ contact lenses were soaked in a 1 ml solution ofnanoparticles in 50:50 ethanol:acetone for a period of 5 min or 24hours. The concentration of particles in the solution was varied fromabout 0.5% to 3%. The compositions of the solutions used in the lensloading are given in Table 4, below. All solutions were prepared byconcentrating the particles formed by polymerization of formulation 1.After 5 min. or 24 hours, the lenses were withdrawn from the solutions,briefly rinsed in pure acetone to remove any surface particles, andsubmerged in DI water.

TABLE 4 Composition of solutions used in lens loading Sample # 1 2 3 4 5Total BHPEA (mg/ml) 8.30 7.01 11.74 25.87 27.61 Reacted BHPEA (mg/ml)7.60 6.46 11.03 22.79 24.79 Unreacted BHPEA (mg/ml) 0.70 0.55 0.71 3.082.82 Ratio React/Unreact BHPEA 10.89 11.64 15.56 7.40 8.79 Total DP(mg/ml) 0.61 0.48 0.77 2.83 3.83 Reacted DP (mg/ml) 0.15 0.15 0.25 0.261.40 Unreacted DP (mg/ml) 0.46 0.33 0.52 2.57 2.43 RatioReacted/Unreacted DP 0.32 0.45 0.47 0.10 0.58Effect of Nanoparticle Loading on UV Blocking

The transmission spectra in the 200 nm to 480 nm range from the controlsilicone hydrogel and those from gels loaded with UV absorbingnanoparticles by addition of nanoparticles particles to thepolymerization mixture are shown in FIGS. 6 to 10. Each figurecorresponds to particles with a fixed loading of the UV absorber and thevarious curves in each figure correspond to different loading of the UVabsorbing nanoparticles in the gels. Average absorbance was calculatedin the UVA, UVB and UVC ranges and these averages are listed in Tables5-8, below. For the UVA range, average absorbance is determined for therange of 315-380 (Table 7) and 315-400 (Table 8).

TABLE 5 Percentage of UVC (below 280 nm) absorbed by nanoparticle ladensilicone gels. % Nanoparticles/gel 5 10 20 % UV dye/nanoparticle 1 98.699.9 2.6 99.0 99.9 99.9 5.9 99.6, 99.9 99.9 (thermo) 9.7 99.9

TABLE 6 Percentage of UVB (280-315 nm) absorbed by nanoparticle ladensilicone gels. % Nanoparticles/gel 5 10 20 % UV dye/nanoparticle 1 79.699.2 2.6 83.6 99.2 99.9 5.9 99.5, 99.9 99.9 (thermo) 9.7 99.9

TABLE 7 Percentage of UVA (315-380 nm) absorbed in nanoparticle ladensilicone gels. % Nanoparticles/gel 5 10 20 % UV dye/nanoparticle 1 61.0095.95 2.6 90.63 98.16 99.36 5.9 98.0, 99.84 99.53 (thermo) 9.7 99.66

TABLE 8 Percentage of UVA (315-400 nm) absorbed in nanoparticle ladensilicone gels. % Nanoparticles/gel 5 10 20 % UV dye/nanoparticle 1 50.8681.82 2.6 67.78 84.00 86.72 5.9 83.09, 91.90 87.24 (thermo) 9.7 94.15

FIG. 6 shows absorption spectra (% absorption) from 200 nm to 480 nm forgels loaded with varying percentage of nanoparticles with about 1% DP inthe particles. The data shows significant reduction in transmittance inthe UV range due to loading DP containing nanoparticles in the gels. Thetransmittance decreases with an increasing in the particle loading, butthe decrease is non linear. The average absorption for the UVA, UVB andUVC ranges listed in Tables 5-8 show that gels loaded with 20% particlesachieve class 1 UV blocking classification. FIG. 6 includes theabsorption spectra from gels loaded with 20% particles that did notcontain DP. These gels also exhibit some reduction in UV transmission,due to the UB blocking from vitamin E encapsulated in the particles.However the UV blocking from particles with vitamin E is significantlyless than that with particles loaded with DP, in addition to vitamin E,due to the higher UV absorption of DP. Although the gels with 20%loading achieved class 1 blocking, the high particle loading couldimpact other lens properties such as modulus, oxygen and ionpermeability, and appliances were designed to achieve class 1 blockingwith lower particle loading.

Nanoparticles with higher DP loading were dispersed in lenses byaddition of the nanoparticles to the polymerization mixture. FIG. 7shows the % transmittance of gels loaded with particles containing 2.6%DP loaded at 5, 10 and 20% w/w in the gels. Gels with 5% particlesblocked UVC almost completely, but blocked only 91% UVB and do notqualify at the class 2 UV blocking classification. On increasing theloading of the particles to 10 and 20% w/w, the transmittance decreasedto 0.8% and ˜0%, respectively in the UVB range. Furthermore, theselenses blocked 84% and 87% in UVA ranges (315-400 nm) respectively, and98 and 99% in the 315-380 nm range, which places the gels with 5% or 10%of the particles in the category of class 1 lenses.

FIG. 8 and FIG. 9 show transmittance plots for gels that are loaded withnanoparticles containing 5.9% and 9.7% DP, respectively. Gels wereprepared with 5 and 10% nanoparticles having 5.9% DP and with 5%nanoparticles having 9.7% DP. In all cases, the gels absorb sufficientUV radiation to be classified as class 1 UV blocking gels. Thus,increasing the amount of DP in the nanoparticles and/or the nanoparticleloading in silicone gels improved the UV blocking. However, the siliconegels formed by polymerization in the presence of UV absorbingnanoparticles become progressively softer, presumably due to thedecrease in the polymerization rates due to the blocking of the UV lightduring polymerization. This effect was overcome by thermalpolymerization to prepare gels having a 5% loading of nanoparticles with5.9% DP using molds in an oven at 80° C. for 24 hours. These gels wereprepared with a 200 μm thickness. The UV blocking from these gels wasadequate for the class 1 classification (FIG. 10). The class 1 or 2classification also depends on the thickness of the contact lenses.However, the UN absorbing nanoparticle approach can be applied to anythickness contact lens by increasing the nanoparticle loading or thefraction of DP in the nanoparticles. The 200 thermally polymerized gelswith 5% nanoparticles having 5.9% DP particles were heated at 100° C.for 2 hours to explore the stability of the UV blocking effect afterexposure to high temperatures. The gels retained class 1 classificationwith only a slight reduction in the UV blocking measured.

Nanoparticles Loaded by Soaking the Appliance in a Solution ofNanoparticles in Ethanol

Silicone gels, prepared as described above, were soaked in 95% ethanolto remove unreacted monomers. To load the nanoparticles into thesilicone gel, each gel was soaked in 3 ml of nanoparticles in ethanol.After soaking for three hours, the gels were withdrawn and submerged in200 ml of DI water for two hours to extract ethanol from the gels. Thegels were withdrawn from the water, gently wiped, and soaked in 5 ml ofDI water for testing. The concentration of nanoparticles in the ethanolsolution was varied from 1 to 10%. The DP loading in the nanoparticlesand the nanoparticle concentration in ethanol are presented in Table 9,below.

TABLE 9 Experimental design of soaking the lenses in solution ofnanoparticles in ethanol Mass % UV Mass UV Vitamin dye per dye E %nanoparticles nanoparticle (mg) (mg) in ethanol 10.2 127 120 2, 5, 1015.8 210 120 1, 2, 5, 10, 20 19.6 280 150 1, 2, 5, 7, 10 28.1 450 150 1,2, 5, 10Mass of Particles Loaded

Silicone hydrogels were soaked in 10.2% DP containing nanoparticles inethanol and the weight gain of the gels was determined after drying. Thenanoparticle loading in the ethanol solutions varied from 2 to 10%. Thedry weight of the gels before and after particle loading and the %increase in gel's weight are listed in Table 10, below. As shown Table10, the increase in gel weight was proportional to the concentration ofnanoparticles in ethanol. The nanoparticles diffused into the lensesduring soaking because the pore size of the gels increases significantlyupon swelling with ethanol.

TABLE 10 Weight change of silicone lenses after soaking in 10.2% DPnanoparticles in ethanol Dry weight Weight of silicone change (g) % %nanoparticle gel after weight in EtOH (g) soaking change 2 0.0235 0.02370.85 5 0.0232 0.0241 3.89 10 0.0240 0.0254 5.83

DP containing nanoparticles were loaded into commercial siliconehydrogel contact lenses by soaking the lenses in an ethanol solution of2% nanoparticles having 5.9% DP. The dry mass of contact lenses beforeand after particle loading and the fractional weight gain of the lensesare given in Table 11, below. Commercial lenses loaded with a largermass of nanoparticles than did laboratory prepared gels. Because contactlenses are typically autoclaved for sterilization, the UV absorbingnanoparticle loaded lenses were autoclaved. The dry weight of the lensesafter autoclaving is included in Table 11. The data shows that particlesthat diffuse into the lenses during soaking are retained in the contactlenses after autoclaving in PBS. Soaking of the UN absorbingnanoparticle laden lenses in PBS at room temperature for extendedperiods did not lead to any leaching of the particles from gels or thecontact lens appliances.

TABLE 11 Weight of commercial contact lenses soaked in 2% ethanolsolutions of 5.9% DP nanoparticles before and after autoclaving UV Dryblocking % of weight laden weight After Control lens (g) lenses changesautoclaving Acuvue Oasys 0.0219 0.0228 4.11 0.0225 O₂ Optix 0.01960.0202 3.06 0.0200 Pure Vision 0.0218 0.0226 3.67 0.0226 Night & Day0.0223 0.0231 3.59 0.0230 Acuvue Advance 0.0200 0.0211 5.5 0.0211Effect of UV Blocking Particles on Transmittance Spectra of the Lenses

The transmission spectra in the 200 nm to 480 nm range from the controlsilicone hydrogel and those from gels loaded with particles by soakingin an ethanol solution of UV absorbing nanoparticles are shown in FIGS.11 to 15. Each figure corresponds to nanoparticles with a single %loading of the UV absorber and the various curves in each figurecorrespond to different loadings of the nanoparticles in ethanol. Theaverage absorbance was calculated for UVA (315-380 nm and 315-400 nm),UVB and UVC ranges. FIG. 11 shows the absorption spectra from gelssoaked in solutions of UV absorbing nanoparticles having 10.2% DP inethanol. The absorbance observed for the control gel is compared withthose from gels soaked in 2%, 5% and 10% nanoparticle in ethanol. Thedata shows significant reduction in transmittance in the UV range due topartitioning of DP containing nanoparticles into the gels during soakingin the ethanol solutions. The nanoparticle loading in the gels isproportional to loading in ethanol but the transmission spectra showonly slight differences. The average absorption in the UVA, UVB and UVCranges are listed in Tables 12-15, below, which indicate that gelssoaked in the solution of nanoparticles having 5% DP absorb nearly allUVB and UVC radiation. The gels block about 84, 87 and 89% of the UVA(315-400 nm) radiation for gels of soaking in 2, 5 and 10% solutions ofthe nanoparticles in ethanol, and block more than 95% of the radiationat 315-380 nm, such that the appliances can be classified as class 1 UVblockers.

TABLE 12 Percentage of UVC (below 280 nm) blocked by nanoparticle ladensilicone gels % nanoparticle in EtOH 1 2 5 7 10 20 % UV dye innanoparticle 10.2 99.5 99.9 99.9 15.8 99.7  99.9 99.9 99.9 99.9 19.699.43 99.9 99.9 99.9 99.9 28.1 99.89 99.9 99.9 99.9

TABLE 13 Percentage of UVB (280-315 nm) blocked by nanoparticle ladensilicone gels % nanoparticle in EtOH 1 2 5 7 10 20 % UV dye innanoparticle 10.2 99.0 99.9 99.9 15.8 99.4 99.9 99.9 99.9 99.9 19.6 99.799.9 99.9 99.9 99.9 28.1 99.9 99.9 99.9 99.9

TABLE 14 Percentage of UVA (315-380 nm) blocked by nanoparticle ladensilicone gels % nanoparticle in EtOH 1 2 5 7 10 20 % UV dye innanoparticle 10.2 99.36 99.82 99.89 15.8 99.45 99.76 99.89 99.9  99.919.6 99.27 99.77 99.9 99.9 99.9  28.1 99.81 99.88 99.9 99.9 

TABLE 15 Percentage of UVA (315-400 nm) blocked by nanoparticle ladensilicone gels % nanoparticle in EtOH 1 2 5 7 10 20 % UV dye innanoparticle 10.2 84.38 87.05 89.38 15.8 85.25 86.21 90.31 92.95 94.3619.6 83.63 86.17 92.10 92.39 93.86 28.1 86.73 88.48 93.54 99.61

To achieve class 1 UV blocking levels with lower nanoparticle loadingsthat improve UV blocking in lenses beyond the class 1 requirements,particles with higher DP content were loaded into gels by soaking inethanol solutions of nanoparticles. FIG. 12 shows the % transmittance ofgels soaked in ethanol solutions of nanoparticles containing 15.8% DP.Gels were soaked in ethanol solutions having different nanoparticleconcentrations (1, 2, 5, 10, and 20%) to prepare gels with differentparticle loadings. The curves in FIG. 12, and the average absorbancevalues in Tables 12-15, above, show that all gels almost completelyblocked UVC, UVB and UVA (315-380 nm) radiation. The gels soaked in 1 or2% solutions block less than 90% UVA (315-400 nm) but the gels soaked in5, 10 and 20% solutions blocked 90.31, 92.95 and 94.36% UVA (315-400 nm)radiation, respectively, and are superior to class 1 UV blockers.

UV absorbing nanoparticle loaded gels clearly display reduced UVtransmittance. To achieve class 1 blocking with minimum nanoparticleloading, gels were loaded with nanoparticles containing 19.6% DP whichshow the transmittance profiles of FIG. 13 for several differentloadings from ethanol solutions having different concentrations ofnanoparticles. The gels loaded with the 19.6% DP particles almostcompletely block UVC, UVB and UVA (315-380 nm). Gels soaked in 7 and 10%solutions display reduced transmittance in the visible range, due to apartial loss in transparency. Gels soaked in 5% solutions block 92.10%UVA (315-400 nm), and can be considered as UV blockers superior to class1 blockers. In FIG. 14, transmittance spectra are shown for gels soakedin ethanol solutions of nanoparticles containing 28.1% DP. Lenses soakedin 10% solutions are partially opaque. Gels soaked in 5% solutions areclass 1 blockers that block some visible light. Gels soaked in 1 and 2%solutions are completely visible light transparent and block sufficientUV radiation to be class 1 classified.

Characterization of Contact Lenses Containing UV Blocking Nanoparticles

The transmittance of the nanoparticle-laden lenses was measured using aUV-Vis spectrophotometer. The lenses were hydrated and mounted on theouter surface of a quartz cuvette. The cuvette was placed in thespectrophotometer and the transmittance was measured from 280 nmwavelength to 380 nm. Transmittance data is used to calculate averageblocking of the UVA and UVB range. For the UVA range, average blockingis determined for the range 316-380 nm and the average blocking for UVBis determined for the range 280-316 nm. The lenses were visually clearand the UV blocking from the lenses is summarized in Table 16, below. AClass 1 lens is required to block 99% of UVB and 90% of UVA light. Thelenses that achieved the required blocking are marked as Class 1 lensesin Table 17, below. Spectra are shown in FIG. 16 for a fewrepresentative cases.

TABLE 16 UV transmittance of nanoparticle loaded lenses Sample # 1 2 3 45 Particles loaded for 5 minutes UVA Transmittance (%) 3.6 5.3 0.5 0.10.1 UVB Transmittance (%) 10.4 13.2 5.2 1.0 1.8 Class I Yes Yes YesParticles loaded for 24 hours UVA Transmittance (%) 0.4 5.6 1.9 1.0 0.5UVB Transmittance (%) 4.5 15.6 11.0 6.8 4.7 Class I Yes Yes Yes

TABLE 17 Concentrations of DP and BHPEA in particle loaded lensescalculated from absorbance spectrum and release into ethanol Sample # 12 3 4 5 Particles loaded for 5 minutes Lens Fit BHPEA (mg/ml) 2.4 1.93.5 7.1 5.3 DP (mg/ml) 1.2 1.1 1.8 6.1 4.0 Release Fit BHPEA (mg/ml) 2.71.3 2.8 4.0 3.6 DP (mg/ml) 1.0 0.6 0.8 2.0 1.6 Particles loaded for 24hours Lens Fit BHPEA (mg/ml) 3.7 1.8 2.3 3.1 3.7 DP (mg/ml) 2.1 0.8 1.11.5 2.0 Release Fit BHPEA (mg/ml) 2.6 1.5 3.0 DP (mg/ml) 0.7 0.3 0.8

Transmittance spectra was converted to the absorbance spectra A=−log₁₀(T/100) and the spectra was then fitted to Equation II by a least squarefit to determine the concentration of DP and BHPEA in the lens. Toobtain the molar absorptivity of DP in the lens, a contact lens wassoaked in a solution of DP in water at a concentration of 0.02 mg/mL.The absorption spectra of the lens were measured and the lens soaked inethanol to extract loaded DP. By measuring the concentration of DP inthe ethanol, the mass of DP extracted was calculated, and used tocalculate the concentration of DP in the lens. By using the measuredabsorbance and the calculated concentration, the molar absorptivity ofDP in the lens was calculated using the Beer Lambert law with a pathlength of 80 microns. The molar absorptivity of BHPEA in the lens wasmeasured in the same manner. By using the molar absorptivities andfitting the absorbance from the particle loaded lenses to Equation II,above, the concentrations of BHPEA and DP in the lens were determined.For validation, particle loaded lenses were soaked in ethanol, and theconcentration of DP and BHPEA was determined in ethanol by measuring theabsorbance spectra. The calculated concentration in ethanol was used tocalculate the concentration in the lens. The concentrations of DP andBHPEA in various particle loaded lenses using both methods are given inTable 5, above.

Release of the UV Blocking Molecules in PBS from the Particle LoadedLenses

Release studies were conducted on the lenses loaded with particles bysoaking the lenses in 3 ml of PBS for 24 hours. The concentrations ofthe UV blockers in PBS were determined using UV-Vis spectrophotometry.The release medium was tested for presence of particles by DLS.Unreacted DP and BHPEA in the lens can be calculated from concentrationdata from the PBS solution if the partition coefficient between PBS andthe lens is known.k=c _(lens) /c _(sol)  Equation III

Partition coefficients for DP and BHPEA were determined by soaking alens with known concentration of BHPEA or DP in a PBS solution. Bydetermining the concentration in the solution before and after soakingthe lens, the mass of BHPEA or DP incorporated into the lens wasdetermined. The concentration of BHPEA or DP in the lens was determinedby weighing the wetted lens and assuming a density of the lens to be 1g/ml. With concentrations in the lens and the solution known, k can bedetermined. If no particles are releasing from the lenses, all releaseinto solution will be from unreacted components and the partitioncoefficients can be used to calculate concentrations of unreactedcomponents inside the lens. The spectra of the release medium are shownin FIG. 17 for a few representative cases. The calculated values of theunreacted concentrations of BHPEA and DP are listed in Table 18, below.

Effect of Autoclaving

Nanoparticles with 15.8% DP were autoclaved at 121° C. for 1 hour andthen loaded into the silicone hydrogel by soaking the gel in ethanolsolution of the nanoparticles. The concentration of nanoparticles inethanol was 1, 5 and 10% (FIG. 15). The transmission spectra from thelenses loaded with autoclaved nanoparticles is equivalent to thoseloaded with non-autoclaved nanoparticles of the same 15.8% DP loadingand the same nanoparticle concentration (FIG. 18). The spectra in FIG.18 are relatively unaffected by autoclaving indicating that DP loadedhighly crosslinked nanoparticles maintain their UV absorption efficiencyupon autoclaving.

Effect of Autoclaving on UV Blocking

Contact lenses are sterilized by autoclaving, so it is necessary todetermine the effect of autoclaving on the UV blocking efficiency of theparticle loaded lenses. Lenses containing the UV blocking particles weresubmerged in boiling water for one hour. Testing before and afterautoclaving showed little change in the transmittance of UV lightthrough the lens, as shown in FIG. 19.

TABLE 18 Concentration of unreacted components in lenses Particlesloaded for 5 minutes Sample # 1 2 3 4 5 Total BHPEA (mg/ml) 2.66 1.282.77 4.04 3.57 Unreacted BHPEA (mg/ml) 0.04 0.04 0.04 0.08 0.09 ReactedBHPEA (mg/ml) 2.62 1.24 2.73 3.96 3.48 Ratio reacted/unreacted 59.7231.09 68.99 49.16 40.52 BHPEA in lens Total DP (mg/ml) 1.03 0.60 0.842.01 1.59 Unreacted DP (mg/ml) 0.18 0.12 0.17 0.43 0.44 Reacted DP(mg/ml) 0.86 0.47 0.67 1.58 1.15 Ratio reacted/unreacted 4.86 3.80 3.863.71 2.63 DBM in lens Particles loaded for 24 hours Sample # 1 2 3 TotalBHPEA (mg/ml) 2.57 1.49 2.97 Unreacted BHPEA (mg/ml) 0.07 0.06 0.08Reacted BHPEA (mg/ml) 2.50 1.43 2.90 Ratio reacted/unreacted 36.54 23.5536.87 BHPEA in lens Total DBM (mg/ml) 0.72 0.26 0.75 Unreacted DBM(mg/ml) 0.06 0.03 0.09 Reacted DBM (mg/ml) 0.66 0.22 0.66 Ratioreacted/unreacted 11.09 6.77 7.25 DBM in lensUV Absorption in Commercial Contact Lenses Loaded with DP ContainingNanoparticles

Commercial contact lenses (Night & Day and Pure Vision) were soaked in 3ml of ethanol solution having 2 and 4% nanoparticles with 19.6% DP. Theprocedures for loading the nanoparticles in the commercial lenses wereas those described above for loading nanoparticles in cured siliconehydrogels. The nanoparticle loaded lenses were autoclaved at 121° C. forone hour. The transmission spectra from the nanoparticle loaded contactlenses, before and after autoclaving, are shown in FIG. 20 and FIG. 21.The % UV blocking is shown in Table 19, below. In all cases, thenanoparticle loaded contact lenses almost completely blocked UVA and UVBradiation. The contact lenses soaked in 2 and 4% solutions blocked 99.85and 99.9% (Night and Day) and 99.9 and 99.9% (Pure Vision), respectivelyand can be classified as class 1 UV blockers. The % absorbance at315-400 nm was 88.57 and 93.82% (Night and Day) and 91.57 and 96.63%(Pure Vision) for lenses soaked in 2 and 4% solutions, respectively.

TABLE 19 UV blocking for 19.6% DP nanoparticle loaded Nigh&Day andPureVision lenses UVA UVA UVC UVB (315-380 nm) (315-400 nm) Night & DayControl 82.3 25.2 36.92 29.58 2% particle in EtOH 99.9 99.9 99.85 88.57After autoclaving 99.9 99.9 99.75 88.00 4% particle in EtOH 99.9 99.999.9 93.82 After autoclaving 99.9 99.9 99.9 90.34 PureVision Control94.4 62.7 32.54 28.34 2% particle in EtOH 99.9 99.9 99.9 91.57 Afterautoclaving 99.9 99.9 99.9 92.37 4% particle in EtOH 99.9 99.9 99.996.63 After autoclaving 99.9 99.9 99.9 94.08

All patents, patent applications, provisional applications, andpublications referred to or cited herein, supra or infra, areincorporated by reference in their entirety, including all figures andtables, to the extent they are not inconsistent with the explicitteachings of this specification.

It should be understood that the examples and embodiments describedherein are for illustrative purposes only and that various modificationsor changes in light thereof will be suggested to persons skilled in theart and are to be included within the spirit and purview of thisapplication.

We claim:
 1. A UV blocking appliance comprising: a hydrophilic orsilicone-hydrogel appliance body; and at least one absorbed UV absorbingcompound, wherein one of the at least one UV absorbing compound is1,3-diphenyl-1,3-propanedione (DP).
 2. The UV blocking appliance ofclaim 1, wherein the at least one UV absorbing compound is bound withina UV absorbing nanoparticle comprising the at least one UV absorbingcompound dispersed in a cross-linked gel, wherein the cross-link densityis sufficiently high to inhibit diffusion of the UV absorbing compoundwithin the cross-linked gel, and wherein the nanoparticles are less than350 nm in diameter to render the UV absorbing compound effectivelyinsoluble in an aqueous solution.
 3. The appliance of claim 2, whereinthe UV absorbing nanoparticles absorb light in the UVA, UVB and UVCregions of the electromagnetic spectrum.
 4. The appliance of claim 2,wherein the UV absorbing nanoparticles absorb light in the UVA and UVBregions of the electromagnetic spectrum.
 5. The appliance of claim 1,wherein the hydrophilic or silicone-hydrogel appliance is a contactlens.
 6. A method for the preparation of a UV blocking appliance ofclaim 2, comprising: providing an appliance comprising a cross-linkedgel, wherein the gel is a hydrophilic gel or silicone-hydrogel;providing a dispersion of a multiplicity of UV absorbing nanoparticlescomprising at least one absorbed UV absorbing compound, wherein one ofthe at least one UV absorbing compound is 1,3-diphenyl-1,3-propanedione(DP), in a non-aqueous solvent; soaking the appliance in the dispersion,wherein the non-aqueous solvent swells the appliance to form a swollenappliance, and wherein the UV absorbing nanoparticles are incorporatedwithin the swollen appliance; and removing the non-aqueous solvent fromthe swollen appliance, wherein the UV absorbing nanoparticles areincorporated to form a UV blocking appliance that is in a non-swollenstate.
 7. The method of claim 6, wherein the non-aqueous solvent isethanol.
 8. The method of claim 6, wherein removing the non-aqueoussolvent comprises removing the non-aqueous solvent as a volatile.
 9. Amethod for the preparation of a UV blocking appliance of claim 1,comprising: providing an appliance comprising a cross-linked gel,wherein the gel is a hydrophilic or silicone-hydrogel; providing asolution of at least one UV absorbing compound in a non-aqueous solvent,wherein one of the at least one UV absorbing compound is1,3-diphenyl-1,3-propanedione (DP); soaking the appliance in thesolution, wherein the non-aqueous solvent swells the appliance to form aswollen appliance, and wherein the UV absorbing compound is incorporatedwithin the swollen appliance; and removing the non-aqueous solvent fromthe swollen appliance, wherein the UV absorbing compound is incorporatedto form a UV blocking appliance that is in a non-swollen state.